Doctoral Dissertation Improvement Award: Effect of Nutrition on Ovarian Aging

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Baishakhi Basu of the University of Washington will conduct research that aims to clarify the mechanisms by which early life and late life undernutrition affects ovarian aging and menopause in Bangladeshi women. The study is inspired by the abundant evidence that the age at which women in resource-poor settings experience menopause is about 6 months earlier than what is found in resource-abundant settings. The underlying biological cause of this discrepancy is unknown. One component of the study will investigate how nutritional stress in fetal life and childhood affects menstrual cycles during the transition that leads to menopause. Another component of the research will investigate whether nutritional stress later in life decreases the age at which menopause occurs. The broader impact of this study will be to elucidate the mechanisms by which nutrition in early life and nutritional stress in later life affects the reproductive biology and function in women. The study will potentially identify which biological mechanisms shorten the reproductive lifespan for women under nutritional stress.The research has two distinct components. The first examines pathways through which fetal life and childhood nutrition may affect the process of ovarian aging. During the transition to menopause, the near depletion of the ovarian follicle pool is reflected by increasingly irregular menstrual cycles. This study hypothesizes that undernutrition during early-life leads to a smaller ovarian follicle pool established in fetal life and/or accelerates the rate at which the follicle pool is reduced. Either effect would result in an earlier depletion of the pool of ovarian follicles and, consequently, an earlier transition to menopause. The research will utilize previously collected menstrual calendars on 2,300 rural Bangladeshi women born before, during and after a severe famine in 1974. The women were born in households that participated in a 1974 socio-economic survey, so the hypothesis is examined by testing for any statistical associations between household wealth in 1974 and the age a woman starts transitioning to menopause. The second component examines whether women experience a type of stress-related amenorrhea (absence of menstrual cycles) that disrupts menstrual cycles before the pool of ovarian follicles is fully depleted (true menopause). This so-called hypothalamic amenorrhea is indistinguishable from, and therefore can be mistaken with, true menopause. To test this idea, Basu will conduct a two month long investigation with the participation of 500 rural Bangladeshi women who have stopped cycling in the past 9-15 months. Urinary specimens provided by the participants will be tested for a hormonal marker that distinguishes true menopause from hypothalamic amenorrhea.